Introduction: Preterm newborns (PTNB) often require sedation and analgesia. Opioids (OPs) and benzodiazepines (BZDs) have been commonly used but are associated with detrimental effects. Dexmedetomidine (Dex) seems a promising alternative. However, data on dosing, length of therapy and adverse events in extreme PTNB are limited. Objective To describe the use of Dex in extreme PTNB in a single academic center Study Design: A retrospective cohort study of PTNB receiving Dex for sedation/analgesia from January 1st, 2010, through December 31st, 2018. At The Cleveland Clinic Children's Hospital an urban tertiary academic center with two Level III and one level IV Neonatal Intensive Care Units (NICU) at different campuses. Inclusion criteria were gestational age (GA) < 36 weeks and receipt Dex for > 2 days. Dex dose and length of treatment were recorded. Clinical response was gauged by reviewing Neonatal Pain, Agitation and Sedation Scale (N-PASS) scores for achievement of the goal (≤ 3). Adverse events were recorded as the incidence of hypotension, bradycardia, and respiratory depression. Results 381 patient charts were reviewed, and 105 patients were included. The birth weight median was 800 grams (range 400–3790); the GA median was 28 weeks (range 22–35). Duration of Dex infusion averaged seven days. Dex dose ranged from 0.2 to 1.2mcg/kg/hour and averaged 0.4mcg/kg/hour. Infants weighing < 1 Kg received a significantly higher Dex dose than infants weighing more or equal to 1 kg (0.5 vs. 0.4mcg/kg/hr, respectively; p = < 0.01). Bradycardia was observed in 35 patients < 1 kg (57%) and in 7 patients > 1 kg (18%) p < 0.01. There was no difference in the incidence of hypotension, fluid resuscitation, or inotropic use between groups defined by birth weight. However, infants < 1 kg required more pharmacological interventions to maintain N-PASS score < 3. Conclusions DEX was well tolerated overall and provided adequate sedation to PTNB in this cohort. This is a report of its use in extreme premature infants, providing guidance of dosages, length of therapy, and possible weaning strategies.